High-Mass MALDI-MS Using Ion Conversion Dynode Detectors: Influence of the Conversion Voltage on Sensitivity and Spectral Quality

  • Simon Weidmann
  • Renato ZenobiEmail author
Research Article


With the development of special ion conversion dynode (ICD) detectors for high-mass matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), the mass-to-charge ratio is no longer a limiting factor. Although these detectors have been successfully used in the past, there is lack of understanding of the basic processes in the detector. We present a systematic study to investigate the performance of such an ICD detector and separate the contributions of the MALDI process from the ones of the ion-to-secondary ion and the secondary ion-to-electron conversions. The performance was evaluated as a function of the voltages applied to the conversion dynodes and the sample amount utilized, and we found that the detector reflects the MALDI process correctly: limitations such as sensitivity or deviations from the expected signal intensity ratios originate from the MALDI process itself and not from the detector.

Graphical abstract


MALDI-ToF-MS High-mass protein analysis Ion conversion dynode Sensitivity Resolution 



The authors thank the initiative (CINA grant) and the Swiss National Science Foundation (grant no. 200020-124663) for financial support, and Nadezhda Nespovitaya for her help with the expression and purification of the MBP polyproteins.


  1. 1.
    Mädler, S., Boeri Erba, E., Zenobi, R.: MALDI-ToF mass spectrometry for studying noncovalent complexes of biomolecules. In: Topics in current chemistry, Springer-Verlag: Berlin/Heidelberg, pp. 1–36 (2012)Google Scholar
  2. 2.
    Nazabal, A., Wenzel, R.J., Zenobi, R.: Immunoassays with direct mass spectrometric detection. Anal. Chem. 78(11), 3562–3570 (2006)CrossRefGoogle Scholar
  3. 3.
    Pimenova, T., Pereira, C.P., Schaer, D.J., Zenobi, R.: Characterization of high molecular weight multimeric states of human haptoglobin and hemoglobin-based oxygen carriers by high-mass MALDI MS. J. Sep. Sci. 32(8), 1224–1230 (2009)CrossRefGoogle Scholar
  4. 4.
    Farmer, T.B., Caprioli, R.M.: Determination of protein–protein interactions by matrix-assisted laser desorption/ionization mass spectrometry. J. Mass Spectrom. 33(8), 697–704 (1998)CrossRefGoogle Scholar
  5. 5.
    Helin, J., Caldentey, J., Kalkkinen, N., Bamford, D.H.: Analysis of the multimeric state of proteins by matrix assisted laser desorption/ionization mass spectrometry after cross-linking with glutaraldehyde. Rapid Commun. Mass Spectrom. 13(3), 185–190 (1999)CrossRefGoogle Scholar
  6. 6.
    Pimenova, T., Nazabal, A., Roschitzki, B., Seebacher, J., Rinner, O., Zenobi, R.: Epitope mapping on bovine prion protein using chemical cross-linking and mass spectrometry. J. Mass Spectrom. 43(2), 185–195 (2008)CrossRefGoogle Scholar
  7. 7.
    Chen, F., Gerber, S., Heuser, K., Korkhov, V.M., Lizak, C., Mireku, S., Locher, K.P., Zenobi, R.: High-mass matrix-assisted laser desorption ionization-mass spectrometry of integral membrane proteins and their complexes. Anal. Chem. 85(7), 3483–3488 (2013)CrossRefGoogle Scholar
  8. 8.
    Beuhler, R.J., Friedman, L.: Threshold studies of secondary-electron emission induced by macro-ion impact on solid-surfaces. Nucl. Inst. Methods 170(1–3), 309–315 (1980)CrossRefGoogle Scholar
  9. 9.
    Geno, P.W., Macfarlane, R.D.: Secondary electron emission induced by impact of low-velocity molecular ions on a microchannel plate. Int. J. Mass Spectrom. Ion Process. 92, 195–210 (1989)CrossRefGoogle Scholar
  10. 10.
    Brunelle, A., Chaurand, P., Della-Negra, S., Le Beyec, Y., Baptista, G.B.: Surface secondary-electron and secondary-ion emission induced by large molecular ion impacts. Int. J. Mass Spectrom. Ion Process. 126, 65–73 (1993)CrossRefGoogle Scholar
  11. 11.
    Wenzel, R.J., Röhling, U., Nazabal, A., Hillenkamp, F.: A detector device for high mass ion detection, a method for analyzing ions of high mass and a device for selection between ion detectors. Internat. Patent WO2009/086642-A1, July 16 (2009)Google Scholar
  12. 12.
    Wenzel, R.J., Matter, U., Schultheis, L., Zenobi, R.: Analysis of megadalton ions using cryodetection MALDI time-of-flight mass spectrometry. Anal. Chem. 77(14), 4329–4337 (2005)CrossRefGoogle Scholar
  13. 13.
    Riek, U., Scholz, R., Konarev, P., Rufer, A., Suter, M., Nazabal, A., Ringler, P., Chami, M., Müller, S.A., Neumann, D., Forstner, M., Hennig, M., Zenobi, R., Engel, A., Svergun, D., Schlattner, U., Wallimann, T.: Structural properties of AMP-activated protein kinase. J. Biol. Chem. 283(26), 18331–18343 (2008)CrossRefGoogle Scholar
  14. 14.
    Weidmann, S., Kemmerling, S., Mädler, S., Stahlberg, H., Braun, T., Zenobi, R.: Ionic liquids as matrices in microfluidic sample deposition for high-mass matrix-assisted laser desorption/ionization mass spectrometry. Eur. J. Mass Spectrom. 18(3), 279–286 (2012)CrossRefGoogle Scholar
  15. 15.
    Chen, F., Mädler, S., Weidmann, S., Zenobi, R.: MALDI-MS detection of noncovalent interactions of single stranded DNA with Escherichia coli single-stranded DNA-binding protein. J. Mass Spectrom. 47(5), 560–566 (2012)CrossRefGoogle Scholar
  16. 16.
    Winograd, N.: The magic of cluster SIMS. Anal. Chem. 77(7), 142 A–149 A (2005)CrossRefGoogle Scholar
  17. 17.
    Fletcher, J.S., Lockyer, N.P., Vickerman, J.C.: Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions. Mass Spectrom. Rev. 30(1), 142–174 (2011)CrossRefGoogle Scholar
  18. 18.
    Weidmann, S., Barylyuk, K., Nespovitaya, N., Mädler, S., Zenobi, R.: A new, modular mass calibrant for high-mass MALDI-MS. Anal. Chem. 85(6), 3425–3432 (2013)CrossRefGoogle Scholar
  19. 19.
    Farmer, T.B., Caprioli, R.M.: Mass discrimination in matrix-assisted laser-desorption ionization time-of-flight mass-spectrometry: a study using cross-linked oligomeric complexes. J. Mass Spectrom. 30(9), 1245–1254 (1995)CrossRefGoogle Scholar
  20. 20.
    Weidmann, S., Mikutis, G., Barylyuk, K., Zenobi, R.: Mass discrimination in high-mass MALDI-MS. J. Am. Soc. Mass Spectrom. 24(9), 1396–1404 (2013)CrossRefGoogle Scholar
  21. 21.
    Strupat, K.: Molecular weight determination of peptides and proteins by ESI and MALDI. In: Burlingame, A.L. (ed.) Methods in enzymology. Elsevier Academic Press: San Diego, pp. 1–36 (2005)Google Scholar
  22. 22.
    Wiza, J.L.: Microchannel plate detectors. Nucl. Inst. Methods 162(1–3), 587–601 (1979)CrossRefGoogle Scholar
  23. 23.
    Andersson, L.P., Grusell, E., Berg, S.: The parallel-plate electron multiplier. J. Phys. E: Sci. Instrum. 12(11), 1015–1022 (1979)CrossRefGoogle Scholar
  24. 24.
    Price, D.: Time-of-flight mass spectrometry. In Cotter, R.J. (ed.) Time-of-flight mass spectrometry; ACS Symposium Series 549, American Chemical Society: Washington, DC pp. 1–15 (1994)Google Scholar
  25. 25.
    Guilhaus, M.: Principles and instrumentation in time-of-flight mass-spectrometry. Physical and instrumental concepts. J. Mass Spectrom. 30(11), 1519–1532 (1995)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2014

Authors and Affiliations

  1. 1.Department of Chemistry and Applied BiosciencesETH ZürichZürichSwitzerland

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